Over the last decade much has been learned regarding the patterning of the central nervous system in the regions of the spinal cord, hindbrain, and midbrain through the study of the HOX cluster genes and several other developmentally regulated transcription and growth factors. Inspite of this, however, little information has been gained regarding the patterning of the anterior-most, forebrain region. The proposed experiments will use the embryologically manipulatable Xenopus system to attempt to fill some of this void and lay a foundation for future studies. These studies will utilize defined anterior markers to precisely determine the degree of patterning in response to the planar and vertical signals of this region. It has been shown previously that early signals from the ventral marginal zone are capable of specifying the anterior neural boundary (Zhang and Jacobson, 1993). The mechanism underlying this specification will be investigated as well as the effects on anterior patterning. The ability of planar signals, from the anterior neural border, ventral and dorsal marginal zones, to pattern these anterior-most regions of the nervous system will be evaluated in whole embryos and modified Keller sandwiches. Vertical signals from the underlying prechordal plate and notochord will be combined in tissue recombinants with the above planar signals in an attempt to recapitulate the normal forebrain pattern and determine the relative contributions of these vertical signals. The results from these experiments will be foundational to further investigations, both within the Grainer and Keller labs as well as within the scientific community.